Rutgers Robert Wood Johnson Medical School, Cardiovascular Institute, New Brunswick, NJ, USA.
J Cardiovasc Pharmacol Ther. 2020 Jul;25(4):291-298. doi: 10.1177/1074248420907256. Epub 2020 Feb 28.
The duration of randomized controlled clinical trials usually is approximately 3 to 5 years although hypercholesterolemia and other risk factors for atherosclerotic cardiovascular disease (ASCVD) are lifelong conditions.
The legacy effect, defined as the persistence of benefit of pharmacologic interventions in clinical trials after the end of the randomized phase when all participants receive active therapy, is used to examine the long-term benefit. We summarize the evidence for the existence of the legacy effect as it pertains to hypercholesterolemia, describe underlying mechanisms, and discuss its relevance to clinical practice.
We examined all published (n = 13) randomized clinical trials of lipid-lowering agents compared to placebo or usual care with follow-up after the randomized phase for the presence or absence of a legacy effect.
A legacy effect was demonstrated in all studies. The current US and European guidelines recommend treatment with high-intensity statins for patients with manifest ASCVD and that individualized approach be used for primary prevention.
The legacy effect results in significant long-term clinical benefits by preventing fatal and nonfatal events. This implies that early therapy would result in lower event rates. Long-term follow-up should be a part of clinical trial design in order to evaluate the presence or absence of a legacy effect.
随机对照临床试验的持续时间通常约为 3 至 5 年，尽管高胆固醇血症和动脉粥样硬化性心血管疾病（ASCVD）的其他危险因素是终身存在的。
遗留效应是指在随机阶段结束后，所有参与者都接受活性治疗时，药物干预的临床获益仍持续存在，用于检验长期获益。我们总结了遗留效应在高胆固醇血症方面的证据，描述了其潜在机制，并讨论了其与临床实践的相关性。
我们检查了所有已发表的（n=13）比较降脂药物与安慰剂或常规治疗的随机临床试验，以观察随机阶段后是否存在遗留效应。
所有研究均显示出遗留效应。目前的美国和欧洲指南建议对有明显 ASCVD 的患者使用高强度他汀类药物治疗，并建议对一级预防采用个体化方法。
遗留效应通过预防致死性和非致死性事件带来了显著的长期临床获益。这意味着早期治疗会降低事件发生率。为了评估遗留效应的存在与否，长期随访应该成为临床试验设计的一部分。
